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| ID | Type | Description | Link |
|---|---|---|---|
| 75N93019C00054 |
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An open-label, dose-ranging influenza challenge study in healthy adult volunteers to determine the optimal infection dose and safety of a recombinant H3N2 (A/Texas/ A/Texas/71/2017 (H3N2, clade 3C3a) influenza strain. The goal of this study is to find a challenge virus dose that is safe and can achieve a symptomatic influenza Attack Rate (AR) that will be sufficiently high for utilization in future vaccine or intervention studies. The optimal dose of the three considered is broadly defined as the minimum challenge virus dose that elicits the highest AR without meeting safety-stopping criteria. Additionally, viral recovery, clinical symptoms, and immune responses over the post-challenge period will be described by challenge dose group. This study will last for up to 1 year depending upon the number of challenge cohorts enrolled given the adaptive dose-escalation design. The populations are healthy males and non-pregnant, non-breastfeeding females aged = 18 and < 46 years of age with a serum HAI antibody titer of \
An open-label, dose-ranging influenza challenge study in healthy adult volunteers to determine the optimal infection dose and safety of a recombinant H3N2 (A/Texas/ A/Texas/71/2017 (H3N2, clade 3C3a) influenza strain. The goal of this study is to find a challenge virus dose that is safe and can achieve a symptomatic influenza Attack Rate (AR) that will be sufficiently high for utilization in future vaccine or intervention studies. The optimal dose of the three considered is broadly defined as the minimum challenge virus dose that elicits the highest AR without meeting safety-stopping criteria. Additionally, viral recovery, clinical symptoms, and immune responses over the post-challenge period will be described by challenge dose group. This study will last for up to 1 year depending upon the number of challenge cohorts enrolled given the adaptive dose-escalation design. The populations are healthy males and non-pregnant, non-breastfeeding females aged = 18 and < 46 years of age with a serum HAI antibody titer of \
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1A | Experimental | 10^4 TCID50of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more subjects in Cohort 1A meet the case definition for influenza, proceed to Cohort 1B. If fewer than 80% of subjects meet the case definition for influenza in Cohort 1A, the dose will escalate to include Cohort 2A. N = 13 |
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| Cohort 1B | Experimental | 10^4 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more subjects in Cohort 1A and 1B meet the case definition for influenza, proceed to Cohort 1C. Cumulatively, if fewer than 80% of subjects in Cohorts 1A and 1B meet the case definition for influenza, the dose will escalate to include Cohort 2A. N = 13 |
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| Cohort 1C | Experimental | 10^4 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and sham sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more of the subjects in Cohorts 1A, 1B, and 1C combined meet the case definition for influenza then the optimal dose of 104 TCID50 will be selected. Cumulatively, if fewer than 80% of subjects in Cohorts 1A, 1B, and 1C meet the case definition for influenza the dose will escalate to include Cohort 2A. N = 13 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Influenza RG-A/Texas/71/2017 (H3N2) Challenge | Biological | RG-A/Texas/71/2017 (H3N2) is an infectious influenza virus and requires handling at BioSafety Level 2. The challenge virus will be administered intranasally in a volume of approximately 0.5 mL per nostril. Intranasal challenge will be carried out using the Intranasal Mucosal Atomization ( MAD Nasa(TM)) Device attached to a 1 mL syringe. |
| Measure | Description | Time Frame |
|---|---|---|
| Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | Symptomatic influenza virus infection is defined as meeting both of the following criteria:
| Day 2 through Day 8 |
| Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Viral shedding status (yes/no) is determined by at least one of: a positive qualitative reverse transcription-polymerase chain reaction (RT-PCR) result from multiplex assay, or a detectable quantitative RT-PCR result. | Day 1 through discharge from the inpatient unit (Day 8 to Day 10) |
| Mean Peak Viral Load (VL) After Challenge | The magnitude of viral shedding is measured via quantitative RT-PCR. Peak VL post-challenge is computed for each participant as the maximum log-10 viral copies/mL. | Day 2 through Day 8 |
| Mean Duration of Viral Shedding | Viral shedding status (yes/no) for each day during the challenge period is determined by at least one of: a positive qualitative RT-PCR result from multiplex assay, or a detectable quantitative RT-PCR result. The duration of shedding for each participant was computed as the number of days from the initial positive NP swab until the day after the final positive NP swab. Intermittent negative results were ignored for this computation. | Day 2 through Day 8 |
| Mean Maximum Cumulative Modified Jackson Score (MJS) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | Adverse events were defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events were collected from Day 1 through Day 57. Adverse events were MedDRA coded. |
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Inclusion Criteria:
Provide written informed consent prior to initiation of any study procedure
Are able to understand and comply with planned study procedures and be available for all study visits
Agree to remain an inpatient for at least 7 days after challenge AND until they have no viral shedding*, determined by qualitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR) beginning on Study Day 6
Healthy* males and non-pregnant, non-breastfeeding females aged > / = 18 and < 46 years of age at enrollment
*Healthy is defined in inclusion criteria #11. NOTE: Female subjects of childbearing potential must have a negative serum pregnancy test at screening, a negative urine pregnancy test upon admission to the confinement unit AND a negative pregnancy test before any Chest x-ray (CXR) (if > / = 7 days have passed since a serum pregnancy test).
Women of childbearing potential* must agree to use or have practiced true abstinence** or use at least one acceptable primary form of contraception* for at least 30 days prior to challenge
Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement with history of documented radiological confirmation test at least 90 days after the procedure).
True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
NOTE: These criteria are applicable to female subjects in a heterosexual relationship AND of child-bearing potential. These criteria do not apply to subjects in a same sex relationship.
Non-habitual smoker* of tobacco, e-cigarettes or marijuana
*Non-habitual smokers are those who smoke no more than four cigarettes, other tobacco products, e-cigarettes (to include vaping and Juuling products) or marijuana in a week and agree not to smoke cigarettes, other tobacco products, e-cigarettes and/or marijuana products during participation in the study.
No self-reported or known history of alcoholism within the last 2 years and agrees to abstain from alcohol for at least one week before admission and throughout the confinement period.
No self-reported or known history of restricted drug use* for at least 30 days prior to challenge and agrees to abstain from restricted drugs for at least one week before admission and throughout the confinement period
Negative drug urine toxicology result on screening (i.e., amphetamines, cocaine, and opiates) and on admission to the confinement unit (i.e., amphetamines, cocaine, and opiates)*
*Select drug use may be allowed at Investigator's discretion (e.g., prescribed amphetamines for ADHD)
Agree not to use the listed prescription or over the counter medications* within 7 days prior to and through confinement period, unless approved by the investigator
*Oseltamivir, zanamivir, peramivir, baloxavir marboxil, amantadine (generic) and rimantadine (Flumadine and generic), aspirin, intranasal steroids, decongestants, antihistamines, and other non-steroidal anti-inflammatory drugs (NSAIDs)
In good health*, and do not have clinically significant medical, psychiatric, chronic or intermittent health conditions including those listed in Exclusion Criteria
*Good health, as determined by medical history, medication use and physical examination to evaluate ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would not affect the assessment of the safety of subjects or the immunogenicity of challenge. These medical diagnoses or conditions should be stable for the last 90 days (no hospitalizations, emergency room (ER) or urgent care for condition (excluding musculoskeletal conditions) and not listed in Exclusion Criteria. Subjects may be on medications only if the condition or disease is stable and not deteriorating, if the medical intervention (such as device or medication) was not available during the maximal inpatient period of time, medications are not listed in the Exclusion Criteria and pose no additional risk to subject safety or assessment of adverse events. This also includes no change in prescription medication, dose or frequency as a result of new symptoms or deterioration of the medical diagnosis or condition in the 90 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome (e.g., lowering of the dosage or frequency), as determined by the site principal investigator (PI) or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572, will not be considered a deviation of this inclusion criterion.
Vital signs as follows:
Eligibility laboratory values White Blood Cell (WBC), Absolute Lymphocyte Count, Hemoglobin (Hgb), Platelets (PLTs), Alanine Transaminase (ALT) and Creatinine(Cr) are within acceptable parameters*
*Labs within normal range or grade 1 abnormalities deemed not clinically significant by a study investigator are considered acceptable
Body mass index (BMI) > 18.5 and < 40 kg/m2 at screening
Other screening tests Electrocardiogram (ECG) and Chest x-ray(CXR) are within normal reference range or not deemed clinically significant by the Principle Investigator(PI) or appropriate sub-investigator*
*Designated clinician licensed to make medical diagnoses and listed on the Form FDA 1572
Negative test for Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) at screening
Negative respiratory virus panel by BIOFIRE(R) FILMARRAY(R) respiratory panel by bioMérieux or by Luminex xTAG(R) on Day -2, and Day -1
Negative RT-PCR test for severe acute respiratory syndrome coronavirus 2(SARS-CoV 2) on screening and Day -2
Hemagglutination Inhibition Test (HAI) antibody titer \
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland, School of Medicine, Center for Vaccine Development and Global Health | Baltimore | Maryland | 21201-4606 | United States |
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Participants were healthy adult volunteers meeting all protocol-defined eligibility criteria. Participants were recruited from the existing cohort that were pre-screened for influenza antibody titers in the screening protocol DMID 20-0004, as well as from other existing participant registries, through advertising, and by word of mouth. Enrollment occurred between 19AUG2021 and 21JUL2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | 10^4 TCID50 Challenge Virus | Cohort 1A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^4 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. Cohorts 1B and 1C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 2A. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 4, 2023 | Aug 30, 2023 |
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| Cohort 2A | Experimental | 10^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 70% or more subjects in Cohort 2A meet the case definition for influenza, proceed to Cohort 1B. If fewer than 70% of subjects meet the case definition for influenza in Cohort 2A, the dose will escalate to include Cohort 3A. N = 13 |
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| Cohort 2B | Experimental | 10^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1.If 70% or more subjects in Cohort 2A and 2B meet the case definition for influenza, proceed to Cohort 2C. Cumulatively, if fewer than 70% of subjects in Cohorts 2A and 2B meet the case definition for influenza, the dose will escalate to include Cohort 3A N = 13 |
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| Cohort 2C | Experimental | 10^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 70% or more of the subjects in Cohorts 2A, 2B, and 2C combined meet the case definition for influenza then the optimal dose of 10^4 TCID50 will be selected. Cumulatively, if fewer than 70% of subjects in Cohorts 2A, 2B, and 2C meet the case definition for influenza the dose will escalate to include Cohort 3A. N = 13 |
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| Cohort 3A | Experimental | 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=17) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If no safety threshold is met (halting conditions) proceed to Cohort 3B. N = 18 |
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| Cohort 3B | Experimental | 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=17) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. N = 18 |
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| Placebo | Other | Sucrose phosphate glutamate (SPG) inoculum |
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The cumulative symptom score from daily component symptoms is computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using the Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes. The maximum cumulative score post-challenge was computed for each participant. |
| Day 2 through Day 8 |
| Number and Percentage of Participants Symptomatic for Influenza. | Participants were categorized as symptomatic if they reported a cumulative symptom score = 6 from daily component symptoms computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using a Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes. | Day 2 through Day 8 |
| Day 1 through Day 29 |
| Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | Adverse events were defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events were collected from Day 1 through Day 57. Adverse events were MedDRA coded. | Day 1 through Day 29 |
| Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | Day 1 through Day 57 |
| Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | Day 1 through Day 57 |
| Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | Day 8, Day 15, and Day 29 |
| Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | Day -1 (baseline), Day 8, Day 15, and Day 29 |
| Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | Day 8, Day 15, and Day 29 |
| Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | Day -1 (baseline), Day 8, Day 15, and Day 29 |
| Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers against HA group 2 stem domains, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | Day 8, Day 15, and Day 29 |
| Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | Day -1 (baseline), Day 8, Day 15, and Day 29 |
| Duke University Trent Drive | Durham | North Carolina | 27710 | United States |
| FG001 |
| 10^5 TCID50 Challenge Virus |
Cohort 2A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^5 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. Cohorts 2B and 2C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 3A. |
| FG002 | 10^6 TCID50 Challenge Virus | Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| FG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 10^4 TCID50 Challenge Virus | Cohort 1A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^4 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. Cohorts 1B and 1C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 2A. |
| BG001 | 10^5 TCID50 Challenge Virus | Cohort 2A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^5 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. Cohorts 2B and 2C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 3A. |
| BG002 | 10^6 TCID50 Challenge Virus | Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| BG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| BMI | Mean | Standard Deviation | kg/m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | Symptomatic influenza virus infection is defined as meeting both of the following criteria:
| The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Count of Participants | Participants | Day 2 through Day 8 |
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| Primary | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Viral shedding status (yes/no) is determined by at least one of: a positive qualitative reverse transcription-polymerase chain reaction (RT-PCR) result from multiplex assay, or a detectable quantitative RT-PCR result. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Count of Participants | Participants | Day 1 through discharge from the inpatient unit (Day 8 to Day 10) |
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| Primary | Mean Peak Viral Load (VL) After Challenge | The magnitude of viral shedding is measured via quantitative RT-PCR. Peak VL post-challenge is computed for each participant as the maximum log-10 viral copies/mL. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. This analysis includes all participants in the Safety population who completed the inpatient period. | Posted | Mean | 95% Confidence Interval | log-10 viral copies/mL | Day 2 through Day 8 |
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| Primary | Mean Duration of Viral Shedding | Viral shedding status (yes/no) for each day during the challenge period is determined by at least one of: a positive qualitative RT-PCR result from multiplex assay, or a detectable quantitative RT-PCR result. The duration of shedding for each participant was computed as the number of days from the initial positive NP swab until the day after the final positive NP swab. Intermittent negative results were ignored for this computation. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. This analysis includes all participants in the Safety population who completed the inpatient period. | Posted | Mean | 95% Confidence Interval | days | Day 2 through Day 8 |
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| Primary | Mean Maximum Cumulative Modified Jackson Score (MJS) | The cumulative symptom score from daily component symptoms is computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using the Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes. The maximum cumulative score post-challenge was computed for each participant. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Mean | 95% Confidence Interval | score on a scale | Day 2 through Day 8 |
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| Primary | Number and Percentage of Participants Symptomatic for Influenza. | Participants were categorized as symptomatic if they reported a cumulative symptom score = 6 from daily component symptoms computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using a Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Count of Participants | Participants | Day 2 through Day 8 |
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| Secondary | Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | Adverse events were defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events were collected from Day 1 through Day 57. Adverse events were MedDRA coded. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Number | events | Day 1 through Day 29 |
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| Secondary | Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | Adverse events were defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events were collected from Day 1 through Day 57. Adverse events were MedDRA coded. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Count of Participants | Participants | Day 1 through Day 29 |
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| Secondary | Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Number | events | Day 1 through Day 57 |
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| Secondary | Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | The Safety population consists of all participants who received study influenza challenge or sham inoculum. | Posted | Count of Participants | Participants | Day 1 through Day 57 |
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| Secondary | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | The Intent-to-Treat population consists of all enrolled participants. | Posted | Count of Participants | Participants | Day 8, Day 15, and Day 29 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | The Intent-to-Treat population consists of all enrolled participants. | Posted | Geometric Mean | 95% Confidence Interval | titer | Day -1 (baseline), Day 8, Day 15, and Day 29 |
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| Secondary | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | The Intent-to-Treat population consists of all enrolled participants. | Posted | Count of Participants | Participants | Day 8, Day 15, and Day 29 |
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| Secondary | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | The Intent-to-Treat population consists of all enrolled participants | Posted | Geometric Mean | 95% Confidence Interval | titer | Day -1 (baseline), Day 8, Day 15, and Day 29 |
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| Secondary | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers against HA group 2 stem domains, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | The Intent-to-Treat population consists of all enrolled participants. | Posted | Count of Participants | Participants | Day 8, Day 15, and Day 29 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group. | The Intent-to-Treat population consists of all enrolled participants | Posted | Geometric Mean | 95% Confidence Interval | titer | Day -1 (baseline), Day 8, Day 15, and Day 29 |
|
Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events and all-cause mortality were collected from Day 1 through Day 57.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10^4 TCID50 Challenge Virus | Cohort 1A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^4 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. Cohorts 1B and 1C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 2A. | 0 | 12 | 0 | 12 | 6 | 12 |
| EG001 | 10^5 TCID50 Challenge Virus | Cohort 2A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^5 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. Cohorts 2B and 2C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 3A. | 0 | 10 | 0 | 10 | 8 | 10 |
| EG002 | 10^6 TCID50 Challenge Virus | Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. | 0 | 36 | 0 | 36 | 17 | 36 |
| EG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. | 0 | 2 | 0 | 2 | 2 | 2 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Vessel puncture site bruise | General disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Vessel puncture site haematoma | General disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA V25.1 | Non-systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA V25.1 | Non-systematic Assessment |
| |
| Blood pressure diastolic decreased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Blood pressure diastolic increased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Blood pressure systolic increased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Heart rate decreased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Heart rate increased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Respiratory rate decreased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Respiratory rate increased | Investigations | MedDRA V25.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA V25.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA V25.1 | Non-systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christopher Woods | Duke University Medical Center | 919-684-7916 | chris.woods@duke.edu |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 11, 2023 | Aug 30, 2023 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 8, 2022 | Sep 30, 2022 | ICF_000.pdf |
| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 | 10^6 TCID50 Challenge Virus | Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| 10^6 TCID50 Challenge Virus |
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| 10^6 TCID50 Challenge Virus |
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 |
| 10^6 TCID50 Challenge Virus |
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 | 10^6 TCID50 Challenge Virus | Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 | 10^6 TCID50 Challenge Virus | Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 |
| 10^6 TCID50 Challenge Virus |
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1.
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 |
| 10^6 TCID50 Challenge Virus |
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1.
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
| OG002 |
| 10^6 TCID50 Challenge Virus |
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. |
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
|
Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1.
| OG003 | Sham Inoculum | From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. |
|
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